Deep brain stimulation halts Parkinson’s disease-related immune dysregulation in the brain and peripheral blood

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity Pub Date : 2024-10-29 DOI:10.1016/j.bbi.2024.10.039

Rhonda L. McFleder , Thomas Musacchio , Johanna Keller , Susanne Knorr , Tobias Petschner , Jia Zhi Chen , Muthuraman Muthuraman , Mohammad Badr , Lisa Harder-Rauschenberger , Fabian Kremer , Selin Asci , Sophie Steinhauser , Ann-Kathrin Karl , Jonathan M. Brotchie , James B. Koprich , Jens Volkmann , Chi Wang Ip

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Abstract

Immune dysregulation in the brain and periphery is thought to contribute to the detrimental neurodegeneration that occurs in Parkinson’s disease (PD). Identifying mechanisms to reverse this dysregulation is key to developing disease-altering therapeutics for this currently incurable disease. Here we utilized the longitudinal data from the Parkinson’s Progression Marker Initiative to demonstrate that circulating lymphocytes progressively decline in PD and can be used to predict future motor symptom progression. Deep brain stimulation (DBS), which is used as a symptomatic treatment, could halt this progressive decline. By analyzing specific immune populations from a second cohort of patients, we could show that DBS causes a shift from the pro-inflammatory CD4⁺ T helper 17 cells driving neurodegeneration to anti-inflammatory CD4⁺ regulatory T cells. RNA-sequencing and immunohistochemistry in the brain of the A53T alpha-synuclein rat model of PD revealed that DBS also decreases neuroinflammation. These data suggest a potential disease-altering role for DBS by halting inflammatory processes.

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深部脑刺激可阻止大脑和外周血中与帕金森病有关的免疫失调。

大脑和外周的免疫失调被认为是导致帕金森病（PD）发生有害神经变性的原因之一。确定逆转这种失调的机制是为这种目前无法治愈的疾病开发改变疾病疗法的关键。在这里，我们利用帕金森病进展标志物倡议（Parkinson's Progression Marker Initiative）的纵向数据证明，循环淋巴细胞在帕金森病中会逐渐减少，并可用于预测未来运动症状的进展。作为对症治疗的脑深部刺激（DBS）可以阻止这种进行性下降。通过分析第二批患者的特定免疫群体，我们可以证明 DBS 会导致驱动神经退行性病变的促炎性 CD4+ T 辅助 17 细胞向抗炎性 CD4+ 调节性 T 细胞转变。A53Tα-突触核蛋白帕金森病大鼠模型脑部的RNA测序和免疫组化显示，DBS还能减少神经炎症。这些数据表明，通过阻止炎症过程，DBS 有可能起到改变疾病的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain, Behavior, and Immunity 医学-免疫学

CiteScore

29.60

自引率

2.00%

发文量

290

审稿时长

28 days

期刊介绍： Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals. As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.